Regulated dynamic subcellular GLUT4 localization revealed by proximal proteome mapping in human muscle cells.

Autor:	Ray A; Department of Biochemistry, Weill Cornell Medicine, New York, NY 10021, USA., Wen J; Department of Biochemistry, Weill Cornell Medicine, New York, NY 10021, USA., Yammine L; Department of Biochemistry, Weill Cornell Medicine, New York, NY 10021, USA., Culver J; Internal Medicine Research Unit , Pfizer Worldwide Research, Development and Medical, Cambridge, MA 02139, USA., Parida IS; Department of Biochemistry, Weill Cornell Medicine, New York, NY 10021, USA., Garren J; Global Biometrics and Data Management , Global Product Development, Pfizer Inc., Cambridge, MA 02139, USA., Xue L; Early Clinical Development Biomedicine AI , Pfizer Worldwide Research, Development and Medical, Cambridge, MA 02139, USA., Hales K; Internal Medicine Research Unit , Pfizer Worldwide Research, Development and Medical, Cambridge, MA 02139, USA., Xiang Q; Target Sciences, Pfizer Inc., New York, NY 10016, USA., Birnbaum MJ; Internal Medicine Research Unit , Pfizer Worldwide Research, Development and Medical, Cambridge, MA 02139, USA., Zhang BB; Internal Medicine Research Unit , Pfizer Worldwide Research, Development and Medical, Cambridge, MA 02139, USA., Monetti M; Internal Medicine Research Unit , Pfizer Worldwide Research, Development and Medical, Cambridge, MA 02139, USA., McGraw TE; Department of Biochemistry, Weill Cornell Medicine, New York, NY 10021, USA.; Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, NY 10021, USA.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2023 Dec 01; Vol. 136 (23). Date of Electronic Publication: 2023 Dec 21.
DOI:	10.1242/jcs.261454
Abstrakt:	Regulation of glucose transport, which is central for control of whole-body metabolism, is determined by the amount of GLUT4 glucose transporter (also known as SLC2A4) in the plasma membrane (PM) of fat and muscle cells. Physiologic signals [such as activated insulin receptor or AMP-activated protein kinase (AMPK)] increase PM GLUT4. Here, we show that the distribution of GLUT4 between the PM and interior of human muscle cells is dynamically maintained, and that AMPK promotes PM redistribution of GLUT4 by regulating exocytosis and endocytosis. Stimulation of exocytosis by AMPK is mediated by Rab10 and the Rab GTPase-activating protein TBC1D4. APEX2 proximity mapping reveals that GLUT4 traverses both PM-proximal and PM-distal compartments in unstimulated muscle cells, further supporting retention of GLUT4 by a constitutive retrieval mechanism. AMPK-stimulated translocation involves GLUT4 redistribution among the same compartments traversed in unstimulated cells, with a significant recruitment of GLUT4 from the Golgi and trans-Golgi network compartments. Our comprehensive proximal protein mapping provides an integrated, high-density, whole-cell accounting of the localization of GLUT4 at a resolution of ∼20 nm that serves as a structural framework for understanding the molecular mechanisms regulating GLUT4 trafficking downstream of different signaling inputs in a physiologically relevant cell type. Competing Interests: Competing interests T.E.M. declares that this project was partially supported by Pfizer Inc. and has nothing else to declare. M.M. and M.J.B. were employees and shareholders of Pfizer Inc. B.B.Z., K.H., Q.X., J.C., J.G. and L.X. are employees and shareholders of Pfizer Inc. A.R., I.S.P., J.W. and L.Y. declare no competing or financial interests. (© 2023. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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